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Low-dose ethanol suppresses 17β-estradiol activity in GH4C1 pituitary tumor cells

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Abstract

The interaction of chronic alcohol consumption with estrogen has been recognized in various tissues; however, the potential mechanism has not been clearly defined. In this study, we made the following observations: (a) 0.01% (v/v) ethanol (corresponding to 1.7 mM) significantly elevated estrogen receptor α (ERα) protein content, stimulated activator protein-1 (AP-1)-dependent ERα transcriptional activities, and ultimately enhanced GH4C1 cells growth in vitro and (b) the same concentration of ethanol suppressed the stimulatory effects of 17β-estradiol (E2; 10 nM) on both cell growth and cellular PRL accumulate through attenuation of ERα actions at both the estrogen response element and the AP-1 site. These observations raise the question as to what extent ethanol influences signal transduction pathways controlled by E2 in experimental medicine and biology.

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Abbreviations

AP-1:

activator protein-1

BrdU:

bromodeoxyuridine

EGF:

epidermal growth factor

ER:

estrogen receptor

ERE:

estrogen response element

EtOH:

ethanol

E2:

17β-estradiol

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

GFP:

green fluorescent protein

GH4:

GH4C1

HPRT:

hypoxanthine phosphoribosyltransferase

IGF-1:

insulin-like growth factor 1

MTT:

methylthiazolyldiphenyl-tetrazolium bromide

PCR:

polymerase chain reaction

PMSF:

phenylmethanesulfonyl fluoride

PRL:

prolactin

RNAi:

RNA interference

shRNA:

short hairpin RNA

SOE:

splicing by overlap extension

TRITC:

tetramethyl rhodamine isothiocyanate

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Acknowledgments

This study was supported by grants to Sheng Cui from the Natural Science Foundation of China (30630011). We thank Dr. Weidong Han (Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing) for kindly providing pSG5-hERα plasmid. The pERE-TK-Luc and pAP1-Luc reporter plasmid were gifts from Prof. Dalong Ma (Chinese National Human Genome Center, Beijing). We also thank Prof. Beate Brand-Saberi (Department of Molecular Embryology, Institute of Anatomy and Cell Biology, Freiburg University, Germany) for the generous gift of the peGFP-H1-shRNA vector. The anti-PRL antibody were obtained through the National Hormone and Peptide Program (NHPP), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Dr. Parlow (NHPP). Monoclonal antibody G3G4 BrdU was developed by Kaufman, S. J. and obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242.

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Authors and Affiliations

  1. State Key Laboratories for AgroBiotechnology, College of Biological Sciences, China Agricultural University, Haidian District Beijing, 100193, People’s Republic of China

    Guoxin Wang, Dawei Chen, Haoshu Luo, Jiali Liu, Xiaowen Ji, Jingjing Fan & Sheng Cui

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  1. Guoxin Wang
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  2. Dawei Chen
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  3. Haoshu Luo
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Correspondence to Sheng Cui.

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Wang, G., Chen, D., Luo, H. et al. Low-dose ethanol suppresses 17β-estradiol activity in GH4C1 pituitary tumor cells. Cell Biol Toxicol 26, 265–277 (2010). https://doi.org/10.1007/s10565-009-9129-7

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